THE NATURAL HISTORY OF OSTEOPENIA IN GIRLS WITH RETT SYNDROME

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 摘要 假设 本研究的目的是描述Rett综合征（RS）女孩和妇女骨量减少的自然史，并确定这些个体中骨脱矿与饮食、内分泌或身体因素之间是否存在相关性。 我们假设：1）RS女童早期骨矿含量的严重丢失持续到成年; 2）BMC的降低与RS女童和妇女的行走能力下降和骨折率增加有关; 3）其骨矿含量的降低与饮食或内分泌因素关系不大。 具体目标 这项研究的具体目标包括： 第一章 确定RS女孩和妇女在整个儿童期和成年期的局部和全身骨矿物质含量（BMC）（以绝对值和z分数测量）是否显著低于健康个体，后者基于年龄、性别和种族特异性规范数据; （二） 确定RS女孩和女性BMC缺陷（以z评分测量）是否与以下因素呈正相关：a）基于既往病史/X线检查记录的骨折临床病史，B）基于Ampere评分的行走能力下降;以及c）存在特异性MECP 2突变 第三章 确定BMC的缺陷（以z分数测量）是否与以下饮食或内分泌因素呈正相关： + 减少膳食钙（Ca）和维生素D摄入量，通过饮食回忆测量 + 抗惊厥药的使用，由临床病史确定并由血清药物水平证实 + 使用避孕药/注射剂，根据临床病史确定 + 使用标准人体测量技术测量身体周长和皮褶，减少局部肌肉（手臂、大腿、小腿）质量 + 血清钙、磷（P）、离子钙、骨特异性碱性磷酸酶、[25-OH]维生素D、[1，25-（OH）2]维生素D、骨钙素、瘦素降低;或完整PTH、D-端肽、尿钙/肌酐输出增加

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. ABSTRACT HYPOTHESIS The purpose of this study is to characterize the natural history of osteopenia in girls and women with Rett Syndrome (RS) relative to normative data and to determine if associations between bone demineralization and dietary, endocrine, or physical factors are present in these individuals. We hypothesize that: 1) the early profound losses of bone mineral content in RS girls persist into adulthood, 2) the reduction in BMC is associated with decreased ambulatory ability and increased fracture rate in RS girls and women, and 3) their reduced bone mineral content bears little relationship with dietary or endocrine factors. SPECIFIC AIMS The specific aims of this study include: 1) To determine if regional and total body bone mineral content (BMC), measured in terms of absolute values and z-scores, by dual-energy x-ray absorptiometry (DXA) is significantly lower throughout childhood and adulthood in RS girls and women than in healthy individuals, the latter based on age-, gender-, and race-specific normative data; 2) To determine if the deficits in BMC, measured as z-scores, of RS girls and women are associated positively with: a) a clinical history of bone fractures, based on previous history/x-ray documentation, b) diminished ambulatory ability, based on their ambulation score; and c) the presence of specific MECP2 mutations 3) To determine if the deficits in BMC, measured as z-scores, are associated positively with the following dietary or endocrine factors: + Reduced dietary calcium (Ca) and vitamin D intakes, measured by dietary recall + The use of anticonvulsants, determined by clinical history and confirmed by serum drug levels + The use of birth control pills/injections, as determined by clinical history + Reduced regional muscle (arm, thigh, calf) mass derived from body circumference and skinfold measurements using standard anthropometric techniques + Decreased serum Ca, phosphorus (P), ionized Ca, bone-specific alkaline phosphatase, [25-OH]vitamin D, [1,25-(OH)2]vitamin D, osteocalcin, leptin; or increased intact PTH, D-teleopeptide, urinary Ca/creatinine output